Carotenoid pigments are presently used to prevent the development of light-sensitivity associated with erythropoietic protoporphyria and certain other skin diseases. Carotenoid pigments have also been shown to be anticarcinogenic in animal models and in some epidemiological studies. The carotenoids which have vitamin A activity also play a significant role as dietary sources of vitamin A, especially in developing countries, where access to synthetic vitamin A is limited. For these reasons it is important to understand the metabolism and functions of the various carotenoids. At present, not much is known about the fate in the body of those pigments with no vitamin A activity. We thus plan to study the absorption, transport and metabolism of two carotenoids with no vitamin A activity - lycopene the principal carotenoid of the tomato, and an important component of the blood carotenoid content of Americans, and canthaxanthin, a pigment used in food coloring, which is used in the treatment of light-sensitive skin diseases and has been shown in animal models to have anti-cancer activity. The absorption and metabolism of beta-carotene will also be studied, to compare it to that of the other two pigments. These studies will utilize C14 labeled carotenoids for studies in rats and monkeys of absorption, blood transport, cellular and intracellular location of pigments, and C13 labeled carotenoids to human volunteers for studies of absorption, transport and excretion in man. We plan also to study the enzyme which cleaves beta-carotene, carotenoid 15, 15' dioxygenase, to determine its distribution in various organs of the rat and monkey, to study its specificity for intact carotenoids, as well as to study the properties of the human enzyme obtained from operative specimens of small intestine. It is well established that the use of compounds labeled with the heavy isotope of carbon (13C) is harmless: the isotope occurs naturally (natural abundance - 1-3%).